辛伐他汀对大鼠平滑肌祖细胞和内皮祖细胞分化的不同影响  

Effects of simvastatin on differentiation of smooth muscle progenitor cells and endothelial progenitor cells in rats

作　　者：张坡[1] 黄岚 刘艳霞[3] 朱鲜阳[1] 韩秀敏[1] 

机构地区：[1]沈阳军区总医院全军心血管研究所先天性心脏病内科,110015 [2]第三军大学新桥医院全军心血管研究所,重庆400037 [3]沈阳军区总医院干二科,110015

出　　处：《国际心血管病杂志》2010年第1期53-56,共4页International Journal of Cardiovascular Disease

基　　金：国家自然科学基金(30270568和30470729)

摘　　要：目的:观察辛伐他汀对平滑肌祖细胞(SPC)和内皮祖细胞(EPC)分化的影响。方法:采用密度梯度离心法获取大鼠骨髓单个核细胞,将其接种在纤维连接素包被培养板,加入不同浓度辛伐他汀(0.01～10μmol/L)培养8d。采用平滑肌肌动蛋白免疫荧光染色鉴定骨髓源性SPC,激光共聚焦显微镜鉴定FITC-UEA-Ⅰ和DiI-acLDL双染阳性细胞为正在分化的EPC,并在倒置荧光显微镜下计数。结果:辛伐他汀显著抑制骨髓单个核细胞分化为SPC。0.01μmol/L辛伐他汀组与对照组SPC数量分别为79±5对85±4(P<0.05)。辛伐他汀显著促进骨髓单个核细胞向EPC分化,其促进作用随辛伐他汀浓度升高而增加,在1.0μmol/L达最大效应。1μmol/L辛伐他汀组与对照组EPC数量分别为87±5对39±4(P<0.01)。结论:辛伐他汀选择性抑制骨髓单个核细胞向SPC分化,促进其向EPC分化,局部应用有促进损伤血管再内皮化和抑制新生内膜过度增生的可能。Objective：To investigate whether simvastatin has different influences on differentiation of rat smooth muscle progenitor cells（SPCs） and endothelial progenitor cells （EPCs） and to identify the compounds that differentially inhibit SPC and EPC differentiation for substantial clinical usefulness. Methods：Total mononuclear cells （MNCs） were isolated from marrow of rats by ficoll density gradient centrifugation, and then the cells were plated on fibronectin-coated culture dishes. SPCs outgrew from the culture of MNCs in SPC medium （the presence of platelet-derived growth factor-BB and basic fibroblast growth factor）, whereas EPCs were obtained in EPC medium （the presence of vascular endothelial growth factor）. SPCs were identified as adherent cells positive for α-SMA by indirect immuno-fluorescent staining. EPCs were characterized as adherent cells double positive for DiLDL- uptake and lectin binding by direct fluorescent staining. MNCs in SPC medium and EPC medium were treated with simvastatin （0.01 ± 10 μmol/L） or vehicle control for 8 d, SPCs and EPCs were assayed with manual counting. Results：Simvastatin potently inhibited MNC differentiation to SPC. At a con centration as low as 0.01 μmol/L for 8 d, simvastatin significantly reduced SPC compared with that in control, （0.01μmol/L simvastatin versus control： 79 ± 5 vs 85± 4, P〈0.05）. Different from SPC, simvastatin dose-dependently increased the number of EPC, with maximum at 1μmol/ L, the number of differentiating EPCs significantly increased （1μmol/L simvastatin versus control： 87±5 vs 39±4, P〈 0.01 ）. Conclusion： Simvastatin of equal dosage displays differential effects on MMC differentiation characterized by inhibiting SPC differentiation but promoting EPC differentiation from the bone marrow MNC.

关 键 词：辛伐他汀 平滑肌祖细胞 内皮祖细胞 分化 

分 类 号：R96[医药卫生—药理学]